Cardiovascular Systems 14 - Coronary heart disease Flashcards
List the risk factors for coronary heart disease
- Modifiable factors (smoking, lipids, blood pressure, diabetes)
- Non-modifiable factors (age, sex and genetic background)
- There is MULTIPLICATION of risk with different factors
List the changes in epidemiology over the last decade, relating to coronary heart disease.
- Reduced hyperlipidaemia
- Reduced hypertension
- Increased obesity and diabetes
- Changing pathology due to altered risk factors
List the interventions for atherosclerosis
- There is a window of opportunity for primary prevention, such as life style changes and risk factor management
- Once complicated, clinical intervention is needed (secondary prevention, catheter based interventions, treatment of heart failure)
List the cell types involved in atherosclerosis
- Vascular endothelial cells
- Monocyte-macrophages
- Vascular smooth muscle cells
- Platelets
- T lymphocytes
Describe the role of vascular endothelial cells in atherosclerosis
- Barrier function
- Leukocyte recruitment
Describe the role of monocyte-macrophages in atherosclerosis
- Foam cell formation
- Cytokine and growth factor release
- Source of free radicals
- Metalloproteinases
Describe the role of vascular smooth muscle cells in atherosclerosis
- Migration and proliferation
- Collagen synthesis
- Remodelling and fibrous cap formation
Describe the role of platelets in atherosclerosis
- Thrombus generation
- Cytokine and growth factor release
Describe the role of t lymphocytes in atherosclerosis
Macrophage activation
How are macrophage subtypes regulated?
By combination of transcription factors binding to regulatory sequences on DNA.
List the two main classes of macrophages
- Inflammatory macrophages are adapted to kill microorganisms
- Resident macrophages are homeostatic, suppressing inflammatory activity
List the functions of resident macrophages
- Suppress inflammatory activity
- Alveolar resident macrophages are involved in surfactant lipid homeostasis
- Osteoclases
- In the spleen there is iron homeostasis
Why are LDLs involved in atherosclerosis formation?
- They are oxidised and modified due to the action of free radicals on LDL, which occurs following binding to proteoglycans in the sub-endothelial layer
- They are highly inflammatory and toxic, found in the vessel wall
Describe the structure of LDLs
- Docking molecule is like an address
- Lipid monolayer is only one molecule thick, similar to a cell membrane
- There is cargo fat for fuel
What can be observed in familial hyperlipidemia?
- Elevated cholesterol, as there is failure to clear LDL
- xanthomas (patches on the skin due to deposition of lipids)
- High risk of early atherosclerosis
What LDL receptors are present in atherosclerosis?
- Scavenger receptors, not under feedback control hoover up modified LDL
- Other LDL receptors are regulated by cholesterol
What are the two macrophage scavenger receptors?
- Receptor A is CD204, binds to oxidised LDL, dead cells and gram +ve bacteria
- Receptor B CD36, binds to oxidised LDL, malaria and dead cells
What enzymes are present in macrophages to modify LDL?
- NADPH oxidase
- Myeloperoxidase
What inflammatory factors are expressed by plaque macrophages?
- Cytokines are protein immune hormones that activate endothelial cell adhesion molecules (VCAM 1)
- Chemokines are small proteins chemoattractant to monocytes (MCP1)
What growth factors are produced by macrophages in the VSMC?
- Platelet derived growth factor (chemotaxis, mitosis, cell survival)
- Transforming growth factor beta (increased collagen synthesis and matrix deposition)
What is the function of metalloproteinases?
- Enzymes that activate each other by proteolysis
- Degrade collagen
- Catalytic mechanism is based on zinc
- Plaque erosion or rupture
List the characteristics of vulnerable plaques.
- Large eccentric lipid-rich necrotic core
- Increased apoptosis
- Reduced collagen
- Thin fibrous cap
- Infiltrate of activated macrophages
Describe the process of macrophage apoptosis in atherosclerosis
- OxLDL derived metabolites are toxic
- Macrophage foam cells have systems to maintain survival following toxic lipid loagind, but once overwhelmed macrophages die via apoptosis
- Macrophage tissue factors and toxic lipids released into the central death zone (lipid necrotic core)
- Thrombogenic and toxic material accumulates until plaque wall rupture
What activates Nuclear factor kappa B?
- Scavenger receptors
- Toll-like receptors
- Cytokine receptors
What inflammatory genes were switched on by NFkB?
- Matrix metalloproteinases
- Inducible nitric oxide synthase
